ApoE4 – The Ancestral Allele

For ApoE4 carriers interested in primal diets and science

Omega-3s, ApoE Genotype and Cognitive Decline (Paper)

with 4 comments

Googling for the rate of APOE4 among Native Americans, I found this paper on omega-3 fats and ApoE4:

The most recent statistics indicate that dietary intake of omega-3 PUFA is insufficient in >95% of Americans. Deficits in omega-3s have been shown to contribute to inflammatory signaling, apoptosis, and neuronal dysfunction in all cause dementia, including Alzheimer’s disease. DHA (22:6[n-3]), specifically, is a critical contributor to cell structure and function in the nervous system, and a recently identified DHA-derived messenger, neuroprotecting D1 (NPD1) has been found to regulate brain cell survival and to promote non-amyloidogenic processing of amyloid precursor protein, thus protecting against Alzheimer’s disease by inhibiting formation of β-amyloid. Studies utilizing omega-3 supplementation to improve cognitive function in elders, however, have had mixed outcomes, an inconsistency which newly published research indicates is related to ApoE genotype. ApoE ε4 carriers have not been able to benefit from omega-3s. This article discusses why and what can be done to enable carriers of the ApoeE ε4 allele to receive the neuroprotective benefits of omega-3s.

The important thing for us is the dietary recommendations.  Some highlights:

ApoE ε4 carriers are the canaries in the mine of the Western way of life. Individuals with this genetic heritage cannot afford the “normal” level of dietary and lifestyle insults typical of life in the modern industrialized world because the ApoE ε4 allele magnifies the risks inherent in the Western diet and lifestyle.

Despite the disproportionately high prevalence of ApoE ε4, cardiovascular disease and diabetes among Native Americans, and the Pima Indians, specifically, research examining a Native American rural population in nearby New Mexico clearly shows that carrying the ApoE ε4 allele does not increase the risk for any of these conditions in people eating a low fat diet and following an active lifestyle.

Another important point the paper makes is that while O3s provide many benefits, they are also vulnerable to oxidative damage.  Depending on the body’s redox state, O3s can be neurotrophic (good for the brain) or neurotoxic (not so good).

The paper seems to conflate a low fat diet with a plant-centered, unprocessed one.  While it has some great information on omega-3s, it doesn’t have much to answer other key primal / e4 fat questions like whether saturated fats are good (as in primal) or bad (because of differences in lipid metabolism for e4s).


Written by patrissimo

February 21, 2013 at 7:13 am

Posted in Diet, Preventative, Research

4 Responses

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  1. Since finding out I am ApoE3/4 I have embraced the current ‘safe starches’ trend in the Paleosphere and moved from a relatively low-carb diet to a more moderate (but still cyclical) approach. My diet is now very inline with the Perfect Health Diet of (not that I actually count/measure/weigh anything) ~15-25% Protein, ~20-30% Carbohydrate (mostly starch from potatoes and white rice), ~50% Fat (mostly MUFA/SAFA with an emphasis on minimising PUFA).

    Still however very much struggling to identify what the optimal changes would/should be based on the current state of evidence though…


    February 21, 2013 at 10:43 am

  2. Not sure how useful a personal anecdote is, but I am E4/E4 and started a LCHF diet about 12 months ago. Typical LFHC diet before that. After 6 months on LCHF my LDL-C had spiked to around 400 (10.4mmol/L) but my HDL had increased as well (from 54 to 77 (1.4mmol/L to 2)) and my trigs were lower (97, down from 132 (1.1mmol/L down from 1.5)).

    The LDL number totally freaked me out, but I continued and tested again after 12 months. HDL improved further (89 or 2.3mmol/L) and trigs as well (88 or 1mmol/L). THe LDL-C number had come down a little (336 or 8.7mmol/L).

    What I found really interesting was my Lp(a) – it had gone from 0.74 g/L on a LFHC diet to 0.5 g/L on LCHF. I know there is still a lot of uncertainty around Lp(a), but if you subscribe to the theory that it is an indicator of oxidized lipids, then I see a drop of 33% to be a very good sign.

    I could be completely wrong or delusional, but I look at my situation like this: LCHF, with a concious effort in minimising PUFAs has resulted in my HDL, triglycerides and Lp(a) improving dramatically. Yes, my LDL is considered “high”, but I don’t see the sense in going back to LFHC (or LFLC) to treat a number. And reading blogs such as Hyperlipid, amongst others, has lead me to believe that LDL is there for a reason, i.e. it is not some evolutionary inbuilt suicide pill.

    So, in terms of the question “what should E4 people eat?”, my personal answer would be “it depends”. Other people who aren’t E4 see similar LDL spikes after eating LCHF and there is so much that we don’t know. For me, I will continue to eat lots of non-PUFA fat, because it feels like the right thing to do and it suits my personal circumstances.

    As time goes by and we learn more, my attitude may change. But for now, fat is my friend.

    Cheers, and thanks for setting up this site.

    St Nick

    February 27, 2013 at 4:03 am

  3. Thank you for this site. The book below outlines suggestions re. APOE and diet:



    April 23, 2013 at 2:02 am

    • Please take no offence, Susannah, but given the author’s reply to this reviewer- http://tinyurl.com/c9pbtru
      it would seem the advice given in the book (that I have not read) should be taken with caution. The study that she said was “ground breaking” is a little weird. http://www.jlr.org/content/35/11/1965.full.pdf

      There were no E4/E4 participants for starters and only 17 E3/E4 people. The low fat diet surely lowered their LDL-C numbers but their HDL was also lower and their triglycerides higher. If she thinks that is a great result, well, she’s easily pleased.

      By all means, seek as many views as possible on the subject, but someone who says they can reverse “Alzheimer’s, gangrene and severe diabetes” with diet is a little suspect.

      Maybe she has it all sorted. Maybe she hasn’t. I haven’t read the book, so I’m only speculating.

      As for the picture on the cover…why? 🙂


      St Nick

      April 25, 2013 at 11:53 pm

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